Biomedical subjects

Ewa Chmielik

Publications and source records attributed to Ewa Chmielik.

7 recordsLinked to original sources

PubMed2006

Association between pathologic response in metastatic lymph nodes after preoperative chemoradiotherapy and risk of distant metastases in rectal cancer: An analysis of outcomes in a randomized trial.

PURPOSE: To compare 5 x 5 Gy preoperative radiotherapy with immediate surgery vs. preoperative chemoradiotherapy (50.4 Gy, 5-fluorouracil, leucovorin) with delayed surgery in a randomized trial for cT3-T4 low-lying rectal cancer. Despite the downstaging effect of chemoradiotherapy, similar long-term outcomes were observed in both groups. METHODS: The Cox model was used to evaluate the prognostic value of ypTN ("yp" denotes that pathologic classification was performed after initial multimodality therapy) categories and the surgical margin status in 291 patients. RESULTS: Disease-free survival (DFS) (hazard ratio [HR] 1.05, 95% confidence interval [CI], 0.73-1.51), distant metastases (HR, 1.17; 95% CI, 0.77-1.78), and local control (HR, 1.45; 95% CI, 0.74-2.84) were similar in both arms. The ypN status was the only independent prognostic factor for DFS (p < 0.001). An interaction (p = 0.016) between N stage and the assigned treatment was demonstrated. For ypN-negative patients, DFS was similar in both arms (HR, 0.83, 95% CI, 0.47-1.48); however, for ypN-positive patients, DFS was worse in the chemoradiotherapy arm (HR, 1.73; 95% CI, 1.07-2.77). The 4-year (median follow-up) DFS rate in N-positive patients was 51% in the 5 x 5-Gy arm vs. 25% in the chemoradiotherapy arm. The corresponding 4-year rates for the incidence of local recurrence and distant metastases were 14% vs. 27% (HR, 1.95; 95% CI, 0.78-4.86) and 38% vs. 68% (HR, 2.05; 95% CI, 1.21-3.48). CONCLUSION: N-positive disease after chemoradiotherapy indicates radiochemoresistance. N-positive disease after 5 x 5 Gy RT includes both radiosensitive and radioresistant tumors, because the interval between radiotherapy and surgery was too short for radiosensitive cancer to undergo necrosis. Thus, the greater risk of distant metastases recorded in the chemoradiotherapy arm suggests that radiochemoresistance of nodal metastases from rectal cancer is associated with a high potential for developing distant metastases.

Adult↗

PubMed2006

Distal intramural spread of rectal cancer after preoperative radiotherapy: the results of a multicenter randomized clinical study.

PURPOSE: To evaluate the extent of distal intramural spread (DIS) after preoperative radiotherapy for rectal cancer. METHODS AND MATERIALS: A total of 316 patients with T(3-4) primary resectable rectal cancer were randomized to receive either preoperative 5x5 Gy radiation with immediate surgery or chemoradiation (50.4 Gy, 1.8 Gy per fraction plus boluses of 5-fluorouracil and leucovorin) with delayed surgery. The slides of the 106 patients who received short-course radiation and of the 86 who received chemoradiation were available for central microscopic evaluation of DIS. RESULTS: The length of DIS did not differ significantly (p = 0.64) between the short-course group and the chemoradiation group and was 0 in 47% vs. 49%; 1 to 5 mm in 41% vs. 42%; 6 to 10 mm in 8% vs. 9%, and greater than 10 mm in 4% vs. 0, respectively. Among the 11 clinically complete responders, DIS was found 1 to 5 mm from the microscopically detected ulceration of the mucosa in 5 patients. The discontinuous DIS was more frequent in the chemoradiation group as compared with the short-course group (i.e., 57% vs. 16% of cases, p < 0.001). CONCLUSIONS: Approximately 1 out of 10 advanced rectal cancers after preoperative radiotherapy or radiochemotherapy was characterized by DIS of over 5 mm. No significant difference was seen in the length of DIS between the 2 groups.

Adult↗

PubMed2006

[Percentage of neoplastic cells in papillary thyroid carcinoma: implications for DNA microarray studies of gene expression profile].

Studies of gene expression profile using DNA microarray technology are usually performed using either tumor-derived sample material or isolated neoplastic cells obtained through microdissection. The scope of information about neoplastic transformation gained from studying profile of gene expression in microdissected samples would be much wider but collection of sufficient amounts of intact RNA is very difficult. A compromise could be reached by relating gene expression profile to percentage of neoplastic cells in the investigated tissue sample. The ratio of neoplastic cells in the investigated sample of papillary thyroid cancer was assessed through evaluation of approximated count of cell number in 10-18 examined image fields. This information was related to gene expression profiles obtained from DNA microarrays. The study involved 40 cases of papillary thyroid cancer; the percentage of PTC cells varied between 20 and 95% and only in half of the cases exceeded 75%. Correct differentiation of tumor and normal sample by means of gene expression profile was possible only when the percentage of tumor cells exceeded 25-30%. Seventeen genes showing the best correlation with the tumor cell numbers were selected and their classification potential was evaluated. Strength of information derived from gene expression profile studies by DNA microarrays in papillary thyroid cancer cells is very reliable and permits distinguishing correctly between normal and neoplastic tissues even when the percentage of cancer cells does not exceed 25-50%. However, the differentiation potential of gene expression profile is not markedly improved by selection of genes showing best correlation with the number of tumor cells.

Adolescent↗

PubMed2005

Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications.

The study looked for an optimal set of genes differentiating between papillary thyroid cancer (PTC) and normal thyroid tissue and assessed the sources of variability in gene expression profiles. The analysis was done by oligonucleotide microarrays (GeneChip HG-U133A) in 50 tissue samples taken intraoperatively from 33 patients (23 PTC patients and 10 patients with other thyroid disease). In the initial group of 16 PTC and 16 normal samples, we assessed the sources of variability in the gene expression profile by singular value decomposition which specified three major patterns of variability. The first and the most distinct mode grouped transcripts differentiating between tumor and normal tissues. Two consecutive modes contained a large proportion of immunity-related genes. To generate a multigene classifier for tumor-normal difference, we used support vector machines-based technique (recursive feature replacement). It included the following 19 genes: DPP4, GJB3, ST14, SERPINA1, LRP4, MET, EVA1, SPUVE, LGALS3, HBB, MKRN2, MRC2, IGSF1, KIAA0830, RXRG, P4HA2, CDH3, IL13RA1, and MTMR4, and correctly discriminated 17 of 18 additional PTC/normal thyroid samples and all 16 samples published in a previous microarray study. Selected novel genes (LRP4, EVA1, TMPRSS4, QPCT, and SLC34A2) were confirmed by Q-PCR. Our results prove that the gene expression signal of PTC is easily detectable even when cancer cells do not prevail over tumor stroma. We indicate and separate the confounding variability related to the immune response. Finally, we propose a potent molecular classifier able to discriminate between PTC and nonmalignant thyroid in more than 90% of investigated samples.

Adolescent↗

PubMed2002

Sex hormone-binding globulin polymorphisms in familial and sporadic breast cancer.

Ovarian steroids are one of the strongest risk factors for breast cancer. Sex hormone-binding globulin (SHBG) binds and transports sex steroids in the blood, regulating their bioavailable fraction and access to target cells. It can also inhibit the estradiol-induced proliferation of breast cancer cells through its membrane receptor. Three coding-region polymorphisms, which lead to an amino acid change, have been reported. We studied the influence of these three polymorphisms on breast cancer risk in three different populations: Polish familial breast cancer cases, 27% of them carrying a BRCA1/BRCA2 mutation, Nordic familial and sporadic breast cancer cases. The reported G to A polymorphism in exon 1 was not found in the 423 analyzed samples. Instead, we found a C to T transition causing an arg to cys amino acid change within the same codon in one Polish breast cancer patient and her daughter. Both of them were heterozygotes for the exon 8 G to A polymorphism as well. They were diagnosed for bilateral breast cancer and carried a BRCA1 mutation (5382insC). Analysis of the tumor samples showed that they had lost the wild-type allele both at exons 1 and 8 of the SHBG gene. Analysis of the other Polish samples showed no correlation of the exon 8 polymorphism to breast cancer, bilateral breast cancer, BRCA1/BRCA2 mutations or age at diagnosis. No association of the exon 8 polymorphism with breast cancer in the Nordic familial or sporadic cases was found. The C to T polymorphism located in exon 4 was rare in all the studied populations (overall allele frequency 0.011). However, in each of the study populations there was a trend for a lower variant allele frequency in cancer cases than in controls. Variant allele frequency in all the breast cancer cases was significantly lower than in all the controls (chi(2) = 5.27, P-value 0.02; odds ratio = 0.23, 95% confidence interval 0.05-0.84).

Adult↗

PubMedDate not supplied

[Gene expression analysis by DNA microarray in papillary thyroid cancer].

In our study we present chosen elements of microarray analysis of gene expression profile in papillary thyroid cancer. The study group included 16 papillary thyroid cancer tissues and 16 corresponding normal tissues. Samples were analyzed on high density oligonucleotide microarrays (GeneChip HG-U133A) which contain 22.000 genes. 110 genes, which had significant changed expression, were selected by MAS 5.0 program. 3 genes were chosen to the deeper analysis: dipeptidylpeptidase 4 (DPP4), fibronectin 1 (FN1), tissue inhibitor of metalloproteinase 1 (TIMP1). DPP4-RNA were absent in normal tissue while in cancer tissue it was detected in large amount. FN1 and TIMP1 expression were detected in normal tissue but markedly increased in papillary thyroid cancer. Among these 3 genes DPP4 seems to be the best molecular marker for papillary thyroid cancer.

Adenosine Deaminase↗

PubMedDate not supplied

[Indications for surgery of thyroid cancer based on bioptate molecular examination].

INTRODUCTION: In differentiated thyroid cancer (DTC) the differentiation between reactive and metastatic lymph nodes is difficult at the early stages of metastasis. The aim of the study was to assess the results of fine needle aspiration (FNA) samples examination by the use of RT-PCR for Tg mRNA. The special attention was directed to the evaluation of specificity of TgRNA estimation. MATERIAL AND METHODS: The group consisted of 193 DTC patients with suspicion of lymph node recurrence and at least one positive RT-PCR result. Thyroglobulin RT-PCR was conducted in residual material left after preparation of cytological smears from FNA specimens. Primer spanning exons 3-5 were used with 39 cycles of PCR. RNA isolation control and cDNA amplification were carried out using GAPDH starters. 308 lymph node biopsies were included. RESULTS: 246 positive results for Tg RNA were observed in the analyzed group, 71.1% confirmed by FNA. Among other 71 results, in which cytological examination did not correspond unequivocally to molecular findings, in 34 metastases were confirmed both by cytological and clinical examination. There were 11 patients operated due to the positive serial molecular examination only. In 10 (91%) of them DTC metastases were confirmed. So, the positive predictive value of the molecular result ranged between 75-89% and the negative one was 100%. CONCLUSIONS: In DTC patients RT-PCR Tg mRNA is helpful in qualification of suspicious lymph nodes to surgery in DTC patients. At the negative cytological finding, the positive molecular result constitutes an indication for early surgery.

Adenocarcinoma, Papillary↗